摘要
目的观察β-淀粉样蛋白(Ap)在APP/Psl转基因小鼠骨组织中的定位分布,探讨AB的异常表达对骨代谢的影响。方法应用免疫组化和免疫荧光技术分别从横切面和纵切面观察9月龄APP/Psl转基因小鼠胫骨近端骨组织中的Aβ的阳性分布,并应用酶联免疫技术和micro.CT对9月龄转基因小鼠和野生型小鼠血清中的TNF-a和IL-6及胫骨近端骨微结构、骨密度进行检测和分析。结果APP/PSl转基因小鼠骨组织横切面和纵切面中的骨小梁和骨细胞周围均可见Aβ的阳性表达;与野生型小鼠各指标相比(32.1±6.8;28.9±4.5;3.2±0.3;3.2±0.3;1229±113),APP/PS1转基因小鼠血清中的肿瘤坏死因子(TNF)-a(42.3±7.4)和IL-6(40.9±6.7)明显升高,而骨小梁数量(1.95±0.22)、骨密度(187±29;1109±104)降低(P〈0.05)。结论Aβ在APP/PS1转基因小鼠骨组织中表达,并和其骨微结构的变化存在一定的相关性,提示AB可能通过影响炎性因子TNF.a和IL-6的变化在APP/PS1转基因小鼠骨质疏松发病过程中起着重要的作用。
Objective To explore the expression pattern of amyloid beta-protein (Aβ) in bone tissue and elucidate its possible effects on bone metabolism of proximal tibia in APP/PS1 transgenic mouse. Methods Immunohistochemisty and immunofluorescence were used to analyze the horizontal and longitudinal sections of proximal tibia in 9-month-old APP/PS1 transgenie mouse. And the tissues of APP/ PS1 transgenic and wild-type mice were harvested to analyze the serum levels of tumor necrosis factor ( TNF- a) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). Micro-computed tomography (micro-CT) was used to analyze the changes of bone microarchitecture and bone mineral density (BMD) of proximal tibia. Results AI3 was expressed in bone trabecular and osteocytes of proximal tibia in APP/PS1 transgenic mouse. As compared with wild-type mice (32. 1 ±6. 8; 28.9 ±4. 5; 3.17 ±0. 26; 3.17 ±0. 26; 1229 ± 113 ), the serum levels of TNF-a(42. 3 ± 7. 4) and IL-6 (40. 9 ± 6. 7 ) of APP/PS1 transgenic mice significantly increased. However bone microarchitecture (1.95 ± 0. 22) and BMD ( 187 ± 29; 1109 ± 104) of proximal tibia were significantly lower on micro-CT (P 〈 0. 05 ). Conclusion AI3 is expressed in bone tissue and it is associated with the changes of bone mineral density. Thus it may play an important role in the pathogenesis of osteoporosis through the changes of TNF-a and IL-6 in APP/PS1 transgenic mouse.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2013年第1期65-68,共4页
National Medical Journal of China
关键词
小鼠
转基因
淀粉样Β蛋白
骨
肿瘤坏死因子
Mice,transgenic
Amyloid beta-protein
Bone
Tumour necrosis factor